Effects of spironolactone in spontaneously hypertensive adult rats subjected to high salt intake

OBJECTIVE:

To evaluate the effect of spironolactone on ventricular stiffness in spontaneously hypertensive adult rats subjected to high salt intake.

INTRODUCTION:

High salt intake leads to cardiac hypertrophy, collagen accumulation and diastolic dysfunction. These effects are partially mediated by cardiac activation of the renin-angiotensin-aldosterone system.

METHODS:

Male spontaneously hypertensive rats (SHRs, 32 weeks) received drinking water (SHR), a 1% NaCl solution (SHR-Salt), or a 1% NaCl solution with a daily subcutaneous injection of spironolactone (80 mg.kg^-1) (SHR-Salt-S). Age-matched normotensive Wistar rats were used as a control. Eight weeks later, the animals were anesthetized and catheterized to evaluate left ventricular and arterial blood pressure. After cardiac arrest, a double-lumen catheter was inserted into the left ventricle through the aorta to obtain in situ left ventricular pressure-volume curves.

RESULTS:

The blood pressures of all the SHR groups were similar to each other but were different from the normotensive controls (Wistar  =  109±2; SHR  =  118±2; SHR-Salt  =  117±2; SHR-Salt-S  =  116±2 mmHg; P<0.05). The cardiac hypertrophy observed in the SHR was enhanced by salt overload and abated by spironolactone (Wistar  =  2.90±0.06; SHR  =  3.44±0.07; SHR-Salt  =  3.68±0.07; SHR-Salt-S  =  3.46±0.05 mg/g; P<0.05). Myocardial relaxation, as evaluated by left ventricular dP/dt, was impaired by salt overload and improved by spironolactone (Wistar  =  -3698±92; SHR  =  -3729±125; SHR-Salt  =  -3342±80; SHR-Salt-S  =  -3647±104 mmHg/s; P<0.05). Ventricular stiffness was not altered by salt overload, but spironolactone treatment reduced the ventricular stiffness to levels observed in the normotensive controls (Wistar  =  1.40±0.04; SHR  =  1.60±0.05; SHR-Salt  =  1.67±0.12; SHR-Salt-S  =  1.45±0.03 mmHg/ml; P<0.05).

CONCLUSION:

Spironolactone reduces left ventricular hypertrophy secondary to high salt intake and ventricular stiffness in adult SHRs.